Affinage · Plasmodium

PMV

PF3D7_1323500 · plasmepsin V

Annotated
2026-09-08
60 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PMV (PF3D7_1323500) is an endoplasmic reticulum-resident aspartic protease that acts as the central maturase of the malaria protein export pathway, co-translationally cleaving the PEXEL/HT motif (RxLxE/Q/D) after the P1 leucine to generate the mature N-terminus required for translocation of cargo into the host erythrocyte (PMID:20130643, PMID:20130644, PMID:24983235). Its catalytic protease domain faces the ER lumen (PMID:25849462), and correct ER residence is itself essential for activity, since mislocalization abolishes PEXEL processing (PMID:20130644). Substrate recognition is exquisitely confined: a P3 arginine and P1 leucine are required, lysine at P3 (as in PfEMP1) or isoleucine at P1 blocks cleavage, and the P1' and P2 residues tune catalytic efficiency—so that PMV processes RIFIN, STEVOR and RESA family proteins but not PfEMP1 or PEXEL-negative exported proteins (PMID:23387285, PMID:25986559). PMV also processes bona fide PEXEL motifs in non-exported proteins such as the parasitophorous vacuole protein UIS2, establishing that it is a more general secretory maturase and that residues of the mature N-terminus (e.g. a P1' aspartate) rather than cleavage per se determine export fate (PMID:38334391). Structurally, PMV adopts a plant-like fold with a malaria-specific helix-turn-helix motif and a unique nepenthesin-1 insert that is essential for activity and allosterically influences catalysis (PMID:26214367, PMID:35952758), with catalytic aspartates D118 and D365 required for turnover (PMID:31108131). PMV is essential for asexual blood-stage viability—conditional knockout arrests parasites at the ring-to-trophozoite transition (PMID:30517136)—and for gametocyte development and mosquito transmission (PMID:31851913), and pharmacological inhibition blocks export, impairs cytoadherence and kills parasites, validating PMV as a directly engaged antimalarial drug target (PMID:24983235, PMID:41329554).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2005 Medium

    Establishing that PMV is an ER-resident integral membrane protein distinct from food-vacuole plasmepsins framed it as an enzyme with an unusual, non-degradative function in the secretory pathway.

    Evidence Subcellular fractionation, immunofluorescence, and pepstatin-binding assays in P. falciparum intraerythrocytic parasites

    PMID:16024107

    Open questions at the time
    • Substrate and catalytic function not yet identified
    • Failure to bind pepstatin A left the enzymatic activity unexplained
  2. 2010 High

    Identifying PMV as the protease that cleaves the PEXEL/HT motif in the ER answered how exported proteins are marked for delivery to the host cell, defining PMV's core biological role.

    Evidence Transgenic chimeric export reporters, mass spectrometry of cleavage products, and conditional mislocalization in P. falciparum, with signal-peptidase N-terminus control

    PMID:20130643 PMID:20130644

    Open questions at the time
    • Full substrate repertoire not defined
    • Mechanism coupling cleavage to translocation unresolved
  3. 2013 High

    Mapping which family proteins are and are not cleaved defined PMV's confined substrate specificity and explained why some exported proteins bypass PEXEL processing.

    Evidence In vitro cleavage assays with recombinant PMV and peptide substrates plus transgenic chimeric expression in P. falciparum

    PMID:23387285

    Open questions at the time
    • Rules for PEXEL-negative export not established
    • Structural basis of specificity not yet resolved
  4. 2014 High

    Pharmacological inhibition plus knockdown/overexpression demonstrated that PMV activity is causally required for protein export, cytoadherence and parasite survival, validating it as a drug target.

    Evidence PEXEL-mimetic inhibitor treatment, PMV knockdown and overexpression, PfEMP1 surface flow cytometry, and growth assays in P. falciparum

    PMID:24983235

    Open questions at the time
    • Whether all lethality stems from export failure vs other roles unclear
    • Resistance mechanisms not yet mapped
  5. 2014 Medium

    In vitro reconstitution of recombinant PMV with kinetic parameters showed the enzyme is active without prosegment removal and clarified its pH optimum and inhibitor profile.

    Evidence Recombinant bacterial expression/refolding and fluorogenic substrate kinetics

    PMID:25447707

    Open questions at the time
    • Recombinant kinetics may not reflect the membrane-embedded ER enzyme
    • Single-lab characterization
  6. 2015 High

    The crystal structure of P. vivax PMV revealed a plant-like fold and a malaria-specific helix-turn-helix motif, explaining strict substrate and inhibitor binding requirements.

    Evidence X-ray crystallography at 2.4 Å with a PEXEL-mimetic inhibitor plus biochemical and growth assays

    PMID:26214367

    Open questions at the time
    • Structure is of the P. vivax ortholog
    • Conformational dynamics during catalysis not captured
  7. 2015 Medium

    Topology mapping placed the catalytic domain in the ER lumen, localizing PEXEL cleavage and N-acetylation to the luminal compartment and excluding cytosolic acetyltransferases.

    Evidence Self-associating split-GFP topology assay in P. falciparum

    PMID:25849462

    Open questions at the time
    • Single method, single lab
    • Identity of the responsible N-acetyltransferase not established
  8. 2016 Medium

    Systematic peptide-variant kinetics quantified how P1' and P2 residues govern cleavage efficiency, refining the substrate rules across P. falciparum and P. vivax orthologs.

    Evidence Recombinant PfPMV and PvPMV fluorogenic substrate assays with PEXEL peptide variants and inhibitor testing

    PMID:25986559 PMID:26795263

    Open questions at the time
    • In vitro peptide efficiencies may not predict in-cell substrate selection
    • S2 pocket differences between species not structurally resolved
  9. 2016 High

    Repositioning the PEXEL motif in KAHRP showed that cleavage is co-translational and depends on PEXEL position relative to the signal sequence, refuting a PI(3)P-based export model.

    Evidence Transgenic P. falciparum expressing PEXEL-repositioned KAHRP constructs with cleavage, export, and ER lipid staining readouts

    PMID:26832821

    Open questions at the time
    • Molecular timing of co-translational recognition not directly visualized
    • Applicability to all substrates untested
  10. 2018 High

    Conditional CRISPR/DiCre knockout gave definitive genetic proof that PMV is essential for asexual viability, pinpointing developmental arrest at the ring-to-trophozoite transition.

    Evidence CRISPR-Cas9 with DiCre conditional excision, growth and phenotypic analysis in P. falciparum

    PMID:30517136

    Open questions at the time
    • Precise molecular cause of arrest not dissected
    • Whether death is solely export-dependent unresolved
  11. 2018 High

    Extending PMV's role to gametocytes showed that PMV-dependent export is required for gametocyte development and transmission competence, broadening its target relevance.

    Evidence PMV inhibitor treatment of gametocyte cultures with cleavage, stage-progression, and mosquito infection assays in P. falciparum

    PMID:31851913

    Open questions at the time
    • Specific gametocyte substrates driving the phenotype not fully catalogued
    • Reliance on pharmacological rather than genetic ablation in sexual stages
  12. 2019 Medium

    Mutagenesis of catalytic residues confirmed D118 and D365 as required for activity, with D365 implicated as the catalytic nucleophile and C178 in substrate recognition.

    Evidence Site-directed mutagenesis of recombinant PfPMV with fluorogenic substrate kinetics

    PMID:31108131

    Open questions at the time
    • Assignment of nucleophile role is inferential from kinetics
    • Role of C178 not structurally confirmed
  13. 2020 Medium

    Tunable knockdown revealed PMV is maintained in large excess and that severe depletion arrests growth immediately after invasion, before export-deficit death, implying two distinct points of vulnerability.

    Evidence TetR-DOZI regulatable knockdown with growth, invasion, and PEXEL processing assays in P. falciparum

    PMID:32069391

    Open questions at the time
    • Molecular basis of the early post-invasion arrest unidentified
    • Substrates responsible for the pre-export phenotype unknown
  14. 2022 High

    Demonstrating that the unique nepenthesin-1 insert is essential for activity identified a malaria-specific structural feature that allosterically controls catalysis and offers a selectivity handle.

    Evidence In-parasite lethal-depletion rescue with insert mutants, disulfide disruption, and molecular dynamics/Markov state modeling in P. falciparum

    PMID:35952758

    Open questions at the time
    • Allosteric mechanism inferred from simulation rather than direct structure
    • Insert conformational states not experimentally trapped
  15. 2024 High

    Showing PMV cleaves PEXEL motifs in non-exported proteins (e.g. UIS2) redefined it as a general secretory maturase and established that downstream N-terminal residues, not cleavage itself, dictate export fate.

    Evidence Chimeric reporter fusions, N-terminal sequencing/MS, and P1' mutagenesis in P. falciparum (peer-reviewed, preceded by bioRxiv preprint)

    PMID:37503245 PMID:38334391

    Open questions at the time
    • Full non-exported substrate set not enumerated
    • Functional consequence of processing non-exported substrates unclear
  16. 2025 High

    Chemoproteomic target engagement plus resistance-mutation genetics confirmed that peptidomimetic antimalarials act directly on PMV, and inhibitor co-crystal structures revealed how to tune PMV-versus-PMX selectivity.

    Evidence Solvent-induced precipitation, thermal profiling, whole-genome sequencing and CRISPR-validated resistance in P. falciparum; X-ray structures of PvPMV-inhibitor complexes with PMV/PMX biochemistry

    PMID:40035447 PMID:41329554

    Open questions at the time
    • Structural work performed on the P. vivax ortholog
    • Clinical relevance of resistance mutations not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular identity of PMV's early post-invasion, export-independent function and the complete catalog of its non-exported substrates remain unresolved.
  • No substrate identified for the pre-export growth arrest seen on severe depletion
  • Full breadth of non-exported PEXEL substrates and their biological roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 PMV (PF3D7_1323500) is an integral membrane protein resident in the endoplasmic reticulum of P. falciparum intraerythrocytic parasites, but not in ERD2-associated Golgi structures; it is expressed throughout asexual development with lowest levels at ring stage; the proregion appears not to be removed following biosynthesis; and unlike food-vacuole plasmepsins, detergent-solubilized PMV does not bind pepstatin A, indicating a distinct function. Subcellular fractionation, solubilization experiments, immunofluorescence microscopy, pepstatin-binding assay Molecular and biochemical parasitology Medium 16024107
2010 PMV is the aspartic acid protease responsible for proteolytic cleavage of the PEXEL/HT motif (RxLxE/Q/D) in the parasite endoplasmic reticulum; PMV cleavage exposes the xE/Q/D residues as the new N-terminus of cargo proteins, which is required for their export into the host erythrocyte; expression of a mature protein with xQ at the N-terminus generated by signal peptidase was not exported, demonstrating that PMV activity is essential and coupled with downstream export events. Transgenic P. falciparum expressing chimeric exported proteins, mass spectrometry identification of cleavage products, signal-peptidase-generated N-terminus control experiment Nature High 20130643 20130644
2010 PMV is an ER-resident aspartic protease with distant homology to mammalian BACE; it recognizes the PEXEL motif and cleaves it at the correct site (after P1 Leu); ER residence is essential for its function, as mislocalization abolishes PEXEL processing. Conditional mislocalization of PMV, in-parasite cleavage assays, sequence homology analysis Nature High 20130644
2013 PMV cleaves N-terminal sequences from RIFIN, STEVOR, and RESA multigene family proteins (the latter containing a relaxed PEXEL, RxLxxE); however, PMV does not cleave PfEMP1 or PEXEL-negative exported proteins SBP-1 or REX-2; lysine at the PEXEL P3 position (present in PfEMP1) blocks PMV activity, and isoleucine at P1 also blocks PMV activity, defining the exquisitely confined substrate specificity of PMV. In vitro cleavage assays with recombinant PMV and peptide substrates, transgenic parasite expression of chimeric proteins Traffic (Copenhagen, Denmark) High 23387285
2014 PMV cleaves the PEXEL motif co-translationally, similar to signal peptidase; pharmacological inhibition of PMV with a PEXEL-mimetic inhibitor causes dose-dependent inhibition of PEXEL processing, blocks protein export including PfEMP1 display on the erythrocyte surface, impairs cytoadherence, and kills parasites at the trophozoite stage; knockdown of PMV enhanced inhibitor sensitivity and overexpression conferred resistance, providing direct evidence that PMV activity is essential for protein export and parasite survival. PEXEL-mimetic inhibitor treatment, PMV knockdown and overexpression in P. falciparum, PEXEL cleavage assays, flow cytometry for surface PfEMP1, parasite growth assays PLoS biology High 24983235
2015 The crystal structure of P. vivax PMV in complex with the PEXEL-mimetic inhibitor WEHI-842 was solved to 2.4-Å resolution, revealing a plant-like fold and a malaria-specific helix-turn-helix motif near the C-terminus that are important for substrate cleavage; the structure explains the strict substrate and inhibitor binding requirements of the enzyme. X-ray crystallography (2.4-Å resolution), biochemical inhibition assays, parasite growth assays Nature structural & molecular biology High 26214367
2015 The catalytic protease domain of PMV faces the endoplasmic reticulum lumen, as determined by self-associating split-GFP topology assay, supporting the model that PEXEL/HT motif cleavage and N-α-acetylation occur in the ER lumen and indicating that cytosolic N-α-acetyltransferases are not candidates for the modification. Split-GFP complementation topology assay in P. falciparum PloS one Medium 25849462
2016 PEXEL processing by PMV occurs co-translationally and is independent of PI(3)P binding; repositioning the PEXEL motif close to the signal sequence in KAHRP prevented PMV cleavage and abolished export, even though the protein retained putative PI(3)P-binding residues; restoring the PEXEL to its original location rescued PMV processing and export, demonstrating that PEXEL position relative to the signal sequence is conserved for co-translational cleavage by PMV. Transgenic P. falciparum expressing PEXEL-repositioned KAHRP constructs, PEXEL cleavage assays, export assays, ER lipid staining Nature communications High 26832821
2014 Recombinant PMV zymogen is enzymatically active; the prosegment is non-essential for refolding or inhibition; mature PMV shows a pH optimum of 5.5–7.0 with Km = 4.6 µM and kcat = 0.24 s⁻¹ at pH 6.0 using a DABCYL-LNKRLLHETQ-E(EDANS) fluorogenic substrate; both zymogen and mature forms are partially inhibited by pepstatin A and certain KNI inhibitors but strongly inhibited by certain metals. Recombinant bacterial expression and refolding, in vitro fluorogenic substrate cleavage assay, kinetic characterization Molecular and biochemical parasitology Medium 25447707
2018 PMV is expressed and active in P. falciparum stage I–II gametocytes; PMV inhibitors block PEXEL processing and export of gametocyte effector proteins, inhibit gametocyte development from stage II–V, and sublethal inhibitor concentrations produce stage V gametocytes that fail to infect mosquitoes, demonstrating that PMV-dependent protein export is essential for gametocyte development and transmission competence. PMV inhibitor treatment of gametocyte cultures, PEXEL cleavage assays, gametocyte stage progression assays, mosquito infection assays Cell reports High 31851913
2018 PMV is an essential gene for P. falciparum asexual blood-stage viability; conditional gene excision using CRISPR-Cas9 combined with DiCre-mediated recombination inactivated the pfpmv gene, causing severe growth defects and developmental arrest early in the ring-to-trophozoite transition, demonstrating that PMV is essential for parasite viability. CRISPR-Cas9 gene editing combined with DiCre conditional excision, parasite growth assays, phenotypic analysis of ring-to-trophozoite development PloS one High 30517136
2020 Stringent post-transcriptional knockdown of PMV using a regulatable system reveals that PMV must be dramatically depleted to affect parasite growth, indicating the parasite maintains PMV in substantial excess; depletion arrests parasite growth immediately after red blood cell invasion, prior to the death caused by exported protein deficit, suggesting PMV inhibitors can halt parasite growth at two distinct points in the life cycle. Post-transcriptional regulatable knockdown system (TetR-DOZI), parasite growth and invasion assays, PEXEL processing assays ACS infectious diseases Medium 32069391
2022 The nepenthesin 1-type insert unique to PMV is essential for parasite growth and PMV activity; mutagenesis of the insert's amino acid sequence or disruption of one of its two disulfide bonds abolishes PMV function and fails to rescue lethal PMV depletion; molecular dynamics and Markov state modeling suggest the insert allosterically affects PMV catalysis. Parasite genetics (lethal PMV depletion rescue with mutant enzymes), site-directed mutagenesis of the nepenthesin insert, molecular dynamics simulations with Markov state modeling The Journal of biological chemistry High 35952758
2024 PMV processes PEXEL motifs in non-exported proteins in addition to exported ones; the parasitophorous vacuole protein UIS2 and other non-exported rhoptry proteins contain bona fide PEXEL motifs that are cleaved by PMV in P. falciparum blood stages; an aspartic acid at the P1' position of the UIS2 PEXEL is permissive for PMV cleavage but blocks export, and mutation of this residue to alanine enables export, demonstrating that features of the mature N-terminus rather than PEXEL cleavage per se determine export. Chimeric reporter fusions expressed in P. falciparum, N-terminal sequencing/mass spectrometry of cleavage products, site-directed mutagenesis of P1' position mSphere High 38334391
2023 PMV processes a non-exported parasitophorous vacuole substrate (UIS2), demonstrating that PMV functions as a more general secretory maturase beyond its established role in marking proteins for export; the identity of residues downstream of the cleavage site controls export fate independently of PMV processing. Chimeric reporter fusions, parasite expression and localization assays (preprint version of the same findings reported in PMID 38334391) bioRxivpreprint Medium 37503245
2019 Recombinant PfPMV catalytic residues D118 and D365 are both required for activity; mutation of D365 has more pronounced effects on catalytic efficiency than D118, suggesting D365 acts as the catalytic nucleophile that activates the water molecule; the unpaired cysteine C178 is partially involved in substrate recognition, as its modification by metal ions reduces activity. Site-directed mutagenesis (D118N, D365N, C178 substitution) of recombinant PfPMV, fluorogenic substrate kinetic assays Molecular and biochemical parasitology Medium 31108131
2016 Substrate specificity studies with recombinant PfPMV show that substitution of Ser with Val or Glu at the P1' position reduces enzyme activity by 75%, and substitution of Ile with Lys or Glu at the P2 position reduces cleavage efficiency by 30%; PfPMV activity is inhibited by PMSF and nelfinavir but not pepstatin A; the P1' and P2 positions of PEXEL substrates are key determinants of PMV catalytic efficiency. Recombinant PfPMV in vitro fluorogenic substrate cleavage assays with PEXEL peptide variants, inhibitor assays Molecular and biochemical parasitology Medium 25986559
2016 Biochemical characterization of P. vivax PMV (Thailand isolate) shows it cleaves PfEMP2-derived peptides more efficiently than HRPII peptides; substitution at P1' Ser to Val or Glu markedly reduces PvPMV activity (as for PfPMV), whereas substitution at P2 with Glu reduces cleavage efficiency by 80% in PvPMV versus only 30% in PfPMV, indicating subtle differences in the S2 binding pocket between species; a four-amino-acid insertion (SVSE at residues 246–249 in PvPMV-Thai) does not interfere with catalytic activity. Recombinant PvPMV expression and refolding, fluorogenic substrate cleavage assays with peptide variants, inhibitor assays Molecular and biochemical parasitology Medium 26795263
2025 Chemoproteomic approaches (solvent-induced protein precipitation and intact-cell thermal profiling) demonstrate direct target engagement of peptidomimetic inhibitors with PMV in P. falciparum parasites; whole-genome sequencing of parasites with reduced peptidomimetic sensitivity revealed a single nucleotide variant within the pmv gene, and reverse genetics validated this mutation as mediating resistance, confirming that the antimalarial activity of peptidomimetics is exerted by directly targeting PMV. Solvent-induced protein precipitation, intact-cell thermal profiling (chemoproteomics), whole-genome sequencing, reverse genetics (CRISPR-validated mutation) ACS infectious diseases High 41329554
2025 X-ray structures of IPF scaffold compounds in complex with PMV (P. vivax) provided structural insights into their binding mode at the active site, revealing avenues to differentially modulate inhibition of PMV versus the related protease plasmepsin X through modifications to the P1 biaryl region. X-ray crystallography of PvPMV-inhibitor complexes, biochemical inhibition assays (PMV and PMX), parasite growth assays The FEBS journal Medium 40035447

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 An aspartyl protease directs malaria effector proteins to the host cell. Nature 255 20130643
2001 Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets. Trends in parasitology 254 11872398
2010 Plasmepsin V licenses Plasmodium proteins for export into the host erythrocyte. Nature 239 20130644
2008 N-terminal processing of proteins exported by malaria parasites. Molecular and biochemical parasitology 144 18534695
2008 Role of the Plasmodium export element in trafficking parasite proteins to the infected erythrocyte. Traffic (Copenhagen, Denmark) 140 19055692
2014 Inhibition of Plasmepsin V activity demonstrates its essential role in protein export, PfEMP1 display, and survival of malaria parasites. PLoS biology 112 24983235
2013 Role of plasmepsin V in export of diverse protein families from the Plasmodium falciparum exportome. Traffic (Copenhagen, Denmark) 108 23387285
2012 Endoplasmic reticulum PI(3)P lipid binding targets malaria proteins to the host cell. Cell 96 22265412
2015 Structural basis for plasmepsin V inhibition that blocks export of malaria proteins to human erythrocytes. Nature structural & molecular biology 83 26214367
2005 Characterization of plasmepsin V, a membrane-bound aspartic protease homolog in the endoplasmic reticulum of Plasmodium falciparum. Molecular and biochemical parasitology 78 16024107
2020 Malaria parasite plasmepsins: More than just plain old degradative pepsins. The Journal of biological chemistry 64 32366462
2004 Common trafficking pathway for variant antigens destined for the surface of the Plasmodium falciparum-infected erythrocyte. Molecular and biochemical parasitology 58 14668007
2016 Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding. Nature communications 57 26832821
2012 Recent advances in plasmepsin medicinal chemistry and implications for future antimalarial drug discovery efforts. Current topics in medicinal chemistry 55 22242846
2014 Transition state mimetics of the Plasmodium export element are potent inhibitors of Plasmepsin V from P. falciparum and P. vivax. Journal of medicinal chemistry 51 25167370
2013 The C-terminal portion of the cleaved HT motif is necessary and sufficient to mediate export of proteins from the malaria parasite into its host cell. Molecular microbiology 38 23279267
2018 Enhanced antimalarial activity of plasmepsin V inhibitors by modification of the P2 position of PEXEL peptidomimetics. European journal of medicinal chemistry 36 29800827
2010 The host targeting motif in exported Plasmodium proteins is cleaved in the parasite endoplasmic reticulum. Molecular and biochemical parasitology 34 20117149
2010 New insights into protein export in malaria parasites. Cellular microbiology 34 20180801
2019 Inhibition of Plasmepsin V Activity Blocks Plasmodium falciparum Gametocytogenesis and Transmission to Mosquitoes. Cell reports 32 31851913
2020 Assessment of Biological Role and Insight into Druggability of the Plasmodium falciparum Protease Plasmepsin V. ACS infectious diseases 29 32069391
2018 Essentiality of Plasmodium falciparum plasmepsin V. PloS one 27 30517136
2015 Picomolar Inhibition of Plasmepsin V, an Essential Malaria Protease, Achieved Exploiting the Prime Region. PloS one 26 26566224
2016 Understanding the structural basis of substrate recognition by Plasmodium falciparum plasmepsin V to aid in the design of potent inhibitors. Scientific reports 21 27531685
2022 A revised mechanism for how Plasmodium falciparum recruits and exports proteins into its erythrocytic host cell. PLoS pathogens 19 35192672
2015 Flap flexibility amongst plasmepsins I, II, III, IV, and V: Sequence, structural, and molecular dynamics analyses. Proteins 19 26146842
2014 The zymogen of plasmepsin V from Plasmodium falciparum is enzymatically active. Molecular and biochemical parasitology 18 25447707
2016 Exploration of the P3 region of PEXEL peptidomimetics leads to a potent inhibitor of the Plasmodium protease, plasmepsin V. Bioorganic & medicinal chemistry 15 27021426
2012 Host targeting of virulence determinants and phosphoinositides in blood stage malaria parasites. Trends in parasitology 15 23084821
2015 Experimental determination of the membrane topology of the Plasmodium protease Plasmepsin V. PloS one 12 25849462
2015 Plasmepsin V shows its carnivorous side. Nature structural & molecular biology 11 26333709
2024 Unveiling potential repurposed drug candidates for Plasmodium falciparum through in silico evaluation: A synergy of structure-based approaches, structure prediction, and molecular dynamics simulations. Computational biology and chemistry 10 38471353
2018 In vitro and in silico studies of naphthoquinones and peptidomimetics toward Plasmodium falciparum plasmepsin V. Biochimie 10 30103899
2015 Plasmodium falciparum Plasmepsin V (PfPMV): Insights into recombinant expression, substrate specificity and active site structure. Molecular and biochemical parasitology 10 25986559
2011 Structural rationale for the recognition of arginine at P₃ in PEXEL motif containing proteins of Plasmodium falciparum by plasmepsin V. Protein and peptide letters 9 21342099
2024 PEXEL is a proteolytic maturation site for both exported and non-exported Plasmodium proteins. mSphere 8 38334391
2023 Identification of a non-exported Plasmepsin V substrate that functions in the parasitophorous vacuole of malaria parasites. mBio 8 38078758
2022 In Silico and In Vitro Antimalarial Screening and Validation Targeting Plasmodium falciparum Plasmepsin V. Molecules (Basel, Switzerland) 8 35566023
2018 Targeting the Plasmodium falciparum plasmepsin V by ligand-based virtual screening. Chemical biology & drug design 8 30320974
2016 The binding landscape of plasmepsin V and the implications for flap dynamics. Molecular bioSystems 8 26965894
2023 Sequence elements within the PEXEL motif and its downstream region modulate PTEX-dependent protein export in Plasmodium falciparum. Traffic (Copenhagen, Denmark) 6 37926971
2014 Plasmepsin V, a secret weapon against malaria. PLoS biology 6 24983361
2013 Imperfect duplicate insertions type of mutations in plasmepsin V modulates binding properties of PEXEL motifs of export proteins in Indian Plasmodium vivax. PloS one 6 23555891
2022 The nepenthesin insert in the Plasmodium falciparum aspartic protease plasmepsin V is necessary for enzyme function. The Journal of biological chemistry 5 35952758
2025 Structure-activity analysis of imino-pyrimidinone-fused pyrrolidines aids the development of dual plasmepsin V and plasmepsin X inhibitors. The FEBS journal 4 40035447
2021 In silico validation of novel inhibitors of malarial aspartyl protease, plasmepsin V and antimalarial efficacy prediction. Journal of biomolecular structure & dynamics 4 33870856
2019 Yield improvement and enzymatic dissection of Plasmodium falciparum plasmepsin V. Molecular and biochemical parasitology 3 31108131
2016 Biochemical characterization of plasmepsin V from Plasmodium vivax Thailand isolates: Substrate specificity and enzyme inhibition. Molecular and biochemical parasitology 3 26795263
2025 Synthesis, Antimalarial Activity and Molecular Dynamics Studies of Pipecolisporin: A Novel Cyclic Hexapeptide with Potent Therapeutic Potential. Molecules (Basel, Switzerland) 2 39860174
2025 Inhibiting catalytic activity of Plasmodium falciparum aspartate protease plasmepsin V: A biochemical approach to malaria intervention. Biochimie 2 41391719
2023 PEXEL is a proteolytic maturation site for both exported and non-exported Plasmodium proteins. bioRxiv : the preprint server for biology 2 37503245
2023 Exploring the Binding Pathway of Novel Nonpeptidomimetic Plasmepsin V Inhibitors. Journal of chemical information and modeling 2 37801405
2025 Deconvolution of the On-Target Activity of Plasmepsin V Peptidomimetics in Plasmodium falciparum Parasites. ACS infectious diseases 1 41329554
2026 Repurposing amide-based drugs unveils inhibition mechanisms of plasmodium falciparum Plasmepsin V enzymatic activity for antimalarial therapy. Bioorganic chemistry 0 41713101
2026 Enhancing the Potency of the Antimalarial Agent, WEHI-601, Through Stereoselective Fluorination. ChemMedChem 0 42174377
2026 Plasmepsins as Antimalarial Drug Targets-Then, Now, and the Future. Medicinal research reviews 0 42227058
2026 Deconstruction of Aspartic Protease Inhibitors Enables Fragment-Based Discovery of Plasmepsin V Inhibitors. ChemMedChem 0 42587390
2026 Identification of a Novel 1,3,4-Thiadiazole-Based Scaffold as a Plasmepsin V Inhibitor. ACS omega 0 42597946
2023 Bioprospection of Selected Plant Secondary Metabolites as Modulators of the Proteolytic Activity of Plasmodium falciparum Plasmepsin V. BioMed research international 0 37388365
2020 Targeting Plasmodium Plasmepsin V: Hitting Two Birds with One Stone. Trends in parasitology 0 31883707